Sl/Sld mouse bone marrow stroma in vitro contains an active radiation-
sensitive inhibitor of normal hemopoiesis
KS Zuckerman, CW Prince and M Ribadeneira
Sl/Sld mice have a defective hemopoietic microenvironment. It has been
assumed, based upon previous studies, that the primary abnormality in these
mice is simply lack of a necessary supportive or inductive material within
the hemopoietic stroma. We used in vitro long-term bone marrow cultures to
characterize further the nature of the hemopoietic microenvironmental
defect in Sl/Sld mice. Sl/Sld mouse bone marrow cells consistently produced
less than 10% of the total hemopoietic cells and multipotent and unipotent
hemopoietic progenitor cells produced in cultures of marrow from normal,
congenic +/+ mice. If fresh Sl/Sld and +/+ marrow cells were mixed prior to
establishing long-term marrow cultures, there was a direct correlation
between number of Sl/Sld cells added and degree of inhibition of +/+
hemopoiesis. A pre- established, confluent Sl/Sld adherent stromal layer
inhibited hemopoiesis by fresh +/+ marrow cells by nearly 70%, as compared
with dishes with irradiated +/+ or no stroma. This inhibitory effect was
abrogated by irradiation of the Sl/Sld stroma prior to addition of the
fresh +/+ marrow cells. Similarly, unirradiated, but not 9 to 200 Gy
irradiated Sl/Sld stroma inhibited proliferation of the factor- dependent
FDC-P1 hemopoietic progenitor cell line. Thus, the Sl/Sld hemopoietic
microenvironment actively inhibits hemopoiesis in vitro, and this
inhibition can be at least partially eliminated by irradiation of the
Sl/Sld stroma.
Volume 68,
Issue 6,
pp. 1201-1206,
12/01/1986
Copyright © 1986 by The American Society of Hematology
